| 1. |
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| 2. |
- Ding, Yuan C, et al.
(author)
-
A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
-
Journal article (peer-reviewed)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 3. |
- Antoniou, Antonis C., et al.
(author)
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A locus on 19p13 modifies risk of breast cancer in BRCA1 mutation carriers and is associated with hormone receptor-negative breast cancer in the general population
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:10, s. 885-892
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Journal article (peer-reviewed)abstract
- Germline BRCA1 mutations predispose to breast cancer. To identify genetic modifiers of this risk, we performed a genome-wide association study in 1,193 individuals with BRCA1 mutations who were diagnosed with invasive breast cancer under age 40 and 1,190 BRCA1 carriers without breast cancer diagnosis over age 35. We took forward 96 SNPs for replication in another 5,986 BRCA1 carriers (2,974 individuals with breast cancer and 3,012 unaffected individuals). Five SNPs on 19p13 were associated with breast cancer risk (P-trend = 2.3 x 10(-9) to Ptrend = 3.9 x 10(-7)), two of which showed independent associations (rs8170, hazard ratio (HR) = 1.26, 95% CI 1.17-1.35; rs2363956 HR = 0.84, 95% CI 0.80-0.89). Genotyping these SNPs in 6,800 population-based breast cancer cases and 6,613 controls identified a similar association with estrogen receptor-negative breast cancer (rs2363956 per-allele odds ratio (OR) = 0.83, 95% CI 0.75-0.92, P-trend = 0.0003) and an association with estrogen receptor-positive disease in the opposite direction (OR = 1.07, 95% CI 1.01-1.14, P-trend = 0.016). The five SNPs were also associated with triple-negative breast cancer in a separate study of 2,301 triple-negative cases and 3,949 controls (Ptrend = 1 x 10(-7) to Ptrend = 8 x 10(-5); rs2363956 per-allele OR = 0.80, 95% CI 0.74-0.87, P-trend = 1.1 x 10(-7)).
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| 4. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
-
In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
-
Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 5. |
- Hatos, Andras, et al.
(author)
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DisProt : intrinsic protein disorder annotation in 2020
- 2020
-
In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 48:D1, s. D269-D276
-
Journal article (peer-reviewed)abstract
- The Database of Protein Disorder (DisProt, URL:https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome.
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| 6. |
- Sartelli, Massimo, et al.
(author)
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Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
In: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Research review (peer-reviewed)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
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| 7. |
- Barbabella, Francesco, Dr. 1984-, et al.
(author)
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Recruitment of Adolescent Young Carers to a Psychosocial Support Intervention Study in Six European Countries : Lessons Learned from the ME-WE Project
- 2023
-
In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 20:6
-
Journal article (peer-reviewed)abstract
- Young carers provide a substantial amount of care to family members and support to friends, yet their situation has not been actively addressed in research and policy in many European countries or indeed globally. Awareness of their situation by professionals and among children and young carers themselves remains low overall. Thus, young carers remain a largely hidden group within society. This study reports and analyses the recruitment process in a multi-centre intervention study offering psychosocial support to adolescent young carers (AYCs) aged 15–17 years. A cluster-randomised controlled trial was designed, with recruitment taking place in Italy, the Netherlands, Slovenia, Sweden, Switzerland and the United Kingdom exploiting various channels, including partnerships with schools, health and social services and carers organisations. In total, 478 AYCs were recruited and, after screening failures, withdrawals and initial dropouts, 217 were enrolled and started the intervention. Challenges encountered in reaching, recruiting and retaining AYCs included low levels of awareness among AYCs, a low willingness to participate in study activities, uncertainty about the prevalence of AYCs, a limited school capacity to support the recruitment; COVID-19 spreading in 2020–2021 and related restrictions. Based on this experience, recommendations are put forward for how to better engage AYCs in research.
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| 8. |
- Beck, Susanne, et al.
(author)
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Examining Open Innovation in Science (OIS): what Open Innovation can and cannot offer the science of science
- 2023
-
In: Innovation: Organization & Management. - : Taylor & Francis (Routledge): SSH Titles. - 2204-0226 .- 1447-9338. ; 25:3, s. 221-235
-
Journal article (peer-reviewed)abstract
- Scholars across disciplines increasingly hear calls for more open and collaborative approaches to scientific research. The concept of Open Innovation in Science (OIS) provides a framework that integrates dispersed research efforts aiming to understand the antecedents, contingencies, and consequences of applying open and collaborative research practices. While the OIS framework has already been taken up by science of science scholars, its conceptual underpinnings require further specification. In this essay, we critically examine the OIS concept and bring to light two key aspects: 1) how OIS builds upon Open Innovation (OI) research by adopting its attention to boundary-crossing knowledge flows and by adapting other concepts developed and researched in OI to the science context, as exemplified by two OIS cases in the area of research funding; 2) how OIS conceptualises knowledge flows across boundaries. While OI typically focuses on well-defined organisational boundaries, we argue that blurry and even invisible boundaries between communities of practice may more strongly constrain flows of knowledge related to openness and collaboration in science. Given the uptake of this concept, this essay brings needed clarity to the meaning of OIS, which has no particular normative orientation towards a close coupling between science and industry. We end by outlining the essay's contributions to OI and the science of science, as well as to science practitioners.
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| 9. |
- Bergquist, Annika, et al.
(author)
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Impact on follow-up strategies in patients with primary sclerosing cholangitis
- 2023
-
In: Liver international (Print). - Chichester, United Kingdom : Wiley-Blackwell Publishing Inc.. - 1478-3223 .- 1478-3231. ; 43:1, s. 127-138
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Evidence for the benefit of scheduled imaging for early detection of hepatobiliary malignancies in primary sclerosing cholangitis (PSC) is limited. We aimed to compare different follow-up strategies in PSC with the hypothesis that regular imaging improves survival.METHODS: We collected retrospective data from 2,975 PSC patients from 27 centers. Patients were followed from the start of scheduled imaging or in case of clinical follow-up from January 1, 2000, until death or last clinical follow-up alive. The primary endpoint was all-cause mortality.RESULTS: A broad variety of different follow-up strategies were reported. All except one center used regular imaging, ultrasound (US) and/or magnetic resonance imaging (MRI). Two centers used scheduled ERCP in addition to imaging for surveillance purposes. The overall HR (CI95%) for death, adjusted for sex, age and start year of follow-up, were 0.61 (0.47-0.80) for scheduled imaging with and without ERCP; 0.64 (0.48-0.86) for US/MRI and 0.53 (0.37-0.75) for follow-up strategies including scheduled ERCP. The lower risk of death remained for scheduled imaging with and without ERCP after adjustment for cholangiocarcinoma (CCA) or high-grade dysplasia as a time-dependent covariate, HR 0.57 (0.44-0.75). Hepatobiliary malignancy was diagnosed in 175 (5.9%) of the patients at 7.9 years follow-up. Asymptomatic patients (25%) with CCA had better survival if scheduled imaging had been performed.CONCLUSIONS: Follow-up strategies vary considerably across centers. Scheduled imaging was associated with improved survival. Multiple factors may contribute to this result including early tumor detection and increased endoscopic treatment of asymptomatic benign biliary strictures.
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| 10. |
- Blunden, Jessica, et al.
(author)
-
State of the Climate in 2012
- 2013
-
In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
-
Journal article (peer-reviewed)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 11. |
- Hanson, Elizabeth, 1961-, et al.
(author)
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Research and Innovation for and with Adolescent Young Carers to Influence Policy and Practice—The European Union Funded “ME-WE” Project
- 2022
-
In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 19:16
-
Journal article (peer-reviewed)abstract
- Young carers are children and adolescents who provide care to other family members or friends, taking over responsibilities that are usually associated with adulthood. There is emerging but still scarce knowledge worldwide about the phenomenon of young carers and the impact of a caring role on their health, social and personal development spheres. This paper provides an overview of the main results from the ME-WE project, which is the first European research and innovation project dedicated to adolescent young carers (AYCs) (15–17 years). The project methods relied on three main activities: (1) a systematization of knowledge (by means of a survey to AYCs, country case studies, Delphi study, literature review); (2) the co-design, implementation and evaluation of a primary prevention intervention addressing AYCs’ mental health (by means of Blended Learning Networks and a clinical trial in six European countries); (3) the implementation of knowledge translation actions for dissemination, awareness, advocacy and lobbying (by means of national and international stakeholder networks, as well as traditional and new media). Project results substantially contributed to a better understanding of AYCs’ conditions, needs and preferences, defined tailored support intervention (resilient to COVID-19 related restrictions), and significant improvements in national and European policies for AYCs.
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| 12. |
- Herman Nap, Henk, et al.
(author)
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D3.1 Consolidated strategy and theory report : ME-WE project deliverable
- 2018
-
Reports (other academic/artistic)abstract
- This deliverable presents the results from three activities to provide an in-depth systematic overview of successful strategies to improve Young Carers (YCs’) mental health and wellbeing. The results form a base for a consolidated strategy and theory for the ME-WE intervention and app to be further developed in WP4. A Delphi study gathered insights into the visibility, awareness, interventions and future needs of YCs in six European countries and on an international level. In addition, a systematic literature review, a general literature review, and social media analyses were carried out. Following these tasks, a rating, ranking and consolidation task was performed to iteratively build a dynamic ranked high impact list with national and international strategies and programmes that can serve as exemplars for the ME-WE intervention.
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| 13. |
- Heslop, James A., et al.
(author)
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Concise Review : Workshop Review: Understanding and Assessing the Risks of Stem Cell-Based Therapies
- 2015
-
In: Stem Cells Translational Medicine. - : Oxford University Press (OUP). - 2157-6564 .- 2157-6580. ; 4:4, s. 389-400
-
Research review (peer-reviewed)abstract
- The field of stem cell therapeutics is moving ever closer to widespread application in the clinic. However, despite the undoubted potential held by these therapies, the balance between risk and benefit remains difficult to predict. As in any new field, a lack of previous application in man and gaps in the underlying science mean that regulators and investigators continue to look for a balance between minimizing potential risk and ensuring therapies are not needlessly kept from patients. Here, we attempt to identify the important safety issues, assessing the current advances in scientific knowledge and how they may translate to clinical therapeutic strategies in the identification and management of these risks. We also investigate the tools and techniques currently available to researchers during preclinical and clinical development of stem cell products, their utility and limitations, and how these tools may be strategically used in the development of these therapies. We conclude that ensuring safety through cutting-edge science and robust assays, coupled with regular and open discussions between regulators and academic/industrial investigators, is likely to prove the most fruitful route to ensuring the safest possible development of new products.
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| 14. |
- Horn, Agnes-Marie, et al.
(author)
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ISSC Committee III.2 - Fatigue and Fracture
- 2009
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In: Proceedings of The 17th International Ship and Offshore Structures Congress (ISSC 2009). - 9788995473016 ; 1, s. 475-586
-
Conference paper (peer-reviewed)abstract
- (COMMITTEE MANDATE) Concern for crack initiation and growth under cyclic loading as well as unstable crack propagation and tearing in ship and offshore structures. Due attention shall be paid to practical application and statistical description of fracture control methods in design, fabrication and service. Consideration is to be given to the suitability and uncertainty of physical models.
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| 15. |
- Horn, Agnes-Marie, et al.
(author)
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ISSC Committee III.2 - Fatigue and fracture
- 2014
-
In: Proceedings of The 18th International Ship and Offshore Structures Congress (ISSC 2012). ; 3, s. 129-151
-
Conference paper (peer-reviewed)abstract
- (COMMITTEE MANDATE) Concern for crack initiation and growth under cyclic loading as well as unstable crack propagation and tearing in ship and offshore structures. Due attention shall be paid to practical application and statistical description of fracture control methods in design, fabrication and service. Consideration is to be given to the suitability and uncertainty of physical models.
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| 16. |
- Josefson, Lennart, 1954, et al.
(author)
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ISSC 2018 Committee V.3 - Materials and Fabrication Technology
- 2018
-
In: Proceedings of the 20th International Ship and Offshore Structures Congress, Specialist Committee Reports. - 9781643680552 ; 2, s. 143-191
-
Conference paper (peer-reviewed)abstract
- The committee shall give an overview about new developments in the field of ship and offshore materials and fabrication techniques with a focus on trends which are highly relevant for practical applications in the industry in the recent and coming years. Particular emphasis shall be given to the impact of welding and corrosion protection techniques for structural performance, and on the development of lighter structures.
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| 17. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 18. |
- Leu, Agnes, et al.
(author)
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Cross-national Analysis of Legislation, Policy and Service Frameworks for Adolescent Young Carers in Europe
- 2022
-
In: Journal of Youth Studies. - : Taylor & Francis Group. - 1367-6261 .- 1469-9680. ; 25:9, s. 1215-1235
-
Journal article (peer-reviewed)abstract
- Despite some national examinations of policy responses for young carers (YCs), this study provides a first comprehensive cross-national comparison of the different legislation, policy and service frameworks that exist to protect and support adolescent young carers (AYCs) in six European countries (Italy, Netherlands, Slovenia, Sweden, Switzerland and United Kingdom) and how these are enacted. Until now, research has focused on estimating numbers of AYCs and the impact of caring tasks. A preliminary examination of policy responses to YCs was followed by expert interviews. Case study analysis of 25 interviews and a cross-national synthesis were undertaken before incorporating feedback from former YCs. Different responses to YCs were found, ranging from protection and support in policy and legislation and a definition for YCs, to a total lack of recognition and support. Findings highlight the potential to extend existing legislation, policy and service frameworks to include AYCs, and the importance of recognising and raising awareness of YCs. Awareness should be raised at all levels of society for example with professionals in health, social and education sectors and the general public. A definition for YCs is needed, so AYCs can self-identify and AYCs should be recognised as an important target group for policy makers.
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| 19. |
- Leu, Agnes, et al.
(author)
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D2.1 Final report on case study analysis of policy, legal and service frameworks in six countries : ME-WE project deliverable
- 2018
-
Reports (other academic/artistic)abstract
- This report provides a first comprehensive transnational comparison of the different legislation, policy and service frameworks that exist to protect and support adolescent young carers (AYCs) in six European countries (Italy, Netherlands, Slovenia, Sweden, Switzerland and United Kingdom) and how these work in practice. Until now, research has primarily focused on estimating the numbers of AYCs and the impact that their caring tasks have on them. Work Package 2 (WP2: National policy, legal and service frameworks) is part of the overall project “Psychosocial support for promoting mental health and wellbeing among adolescent young carers in Europe” (ME-WE), funded by the European Union (Horizon 2020).
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| 20. |
- Leu, Agnes, et al.
(author)
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The 2021 cross-national and comparative classification of in-country awareness and policy responses to ‘young carers’
- 2023
-
In: Journal of Youth Studies. - : Taylor & Francis Group. - 1367-6261 .- 1469-9680. ; 26:5, s. 619-636
-
Journal article (peer-reviewed)abstract
- Many children under the age of 18 are drawn into unpaid caring roles because they live in families where there is chronic illness, mental health problems or substance misuse, and because other alternatives are not available. Many of these children, widely referred to as ‘young carers’, provides regular and significant amounts of care, often ‘hidden’ because of the absence of awareness by professionals in the fields of education, health and social care. While there are some positive outcomes for children, published research also shows that children’s caring tasks can have negative outcomes, especially during the transition between school and further/higher education and paid work. This paper presents an overview, cross-national and comparative analysis of the different legislation, policy and service frameworks to support young carers in a number of countries. It utilises a qualitative assessment approach and a 7-point classification to understand the state of development and progress since 2017. While the legislation, policy and service frameworks differ significantly among the observed countries, an international and collaborative research network has emerged in the last five years. This plays a vital role as a driver for increasing the awareness of young carers and further national and cross-national policy developments in the future.
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| 21. |
- Lewis, Feylyn Mercedies, et al.
(author)
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The first cross-national study of adolescent young carers aged 15–17 in six European countries
- 2023
-
In: International Journal of Care and Caring. - : Policy Press. - 2397-8821 .- 2397-883X. ; 7:1, s. 6-32
-
Journal article (peer-reviewed)abstract
- For the first time, this article will provide a cross-national profile of adolescents who provide unpaid care to their ill or disabled family members in six European countries with varied levels of awareness, policy and service provision regarding adolescent young carers. Utilising an online survey, 2,099 adolescent young carers were identified in Italy, the Netherlands, Slovenia, Sweden, Switzerland and the UK. This article focuses on the impact of unpaid care on their mental health, well-being, physical health and education. Their preferences for informal and formal support were also examined. These groundbreaking findings help promote a ‘rights’ approach to adolescent young carers, which can serve as a critical driver for supportive policy creation on both a country-specific and pan-European level.
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| 22. |
- Matta, Michèle, et al.
(author)
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Dietary intake of trans fatty acids and breast cancer risk in 9 European countries
- 2021
-
In: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 19:1
-
Journal article (peer-reviewed)abstract
- Background: Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results: After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06–1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01–1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03–1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01–1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions: These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.
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| 23. |
- Nap, Henk Herman, et al.
(author)
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The awareness, visibility and support for young carers across Europe : a Delphi study
- 2020
-
In: BMC Health Services Research. - : BioMed Central. - 1472-6963. ; 20:1, s. 1-16
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Journal article (peer-reviewed)abstract
- BackgroundAcross Europe, young carers (YCs) and their need for support receive limited attention in the media, policy and empirical research, even though, similar to adult carers, they also provide care to ill family members. The Delphi study, a qualitative research methodology, which provides the focus for this article, had the overall aim of exploring existing successful strategies to support YCs. Compared to YCs, even less is known about adolescent young carers (AYCs), a group that is in a critical life transition phase. The study forms part of an EU Horizon 2020 funded research project on AYCs aged 15-17years old.MethodsA two-round Delphi study was conducted with 66 experts on YCs from 10 European countries. Topics included: (i) visibility and awareness-raising of YCs at local, regional, and national levels, (ii) current interventions to support YCs, and (iii) future strategies to support YCs.ResultsExperts reported a lack of visibility and awareness about YCs in general, and AYCs in particular. Although awareness is slowly increasing in most countries, with the UK ranked highest, experts acknowledged that it remains challenging to identify YCs in many countries. Furthermore, the level and type of support available for YCs differs, with most countries mainly offering support on a local level. Diverse views were expressed regarding future strategies to support YCs. Experts highlighted the importance of specific legislation to formalise the rights of YCs, and the issue of whether young people should be safeguarded from caregiving or if this should be considered part of regular family life. They also emphasised the relevance of available integrated support services for YCs, including schools, family, health and social care.ConclusionsIn most European countries, there is a lack of awareness and visibility on YCs. Identification of YCs is a crucial first step and there is need for a common definition of YCs, together with greater opportunities for young adults to identify themselves as YCs.
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| 24. |
- Neugart, Susanne, et al.
(author)
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A synchronized, large-scale field experiment using Arabidopsis thaliana reveals the significance of the UV-B photoreceptor UVR8 under natural conditions
- 2024
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In: Plant, Cell and Environment. - : Blackwell Publishing. - 0140-7791 .- 1365-3040.
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Journal article (peer-reviewed)abstract
- This study determines the functional role of the plant ultraviolet-B radiation (UV-B) photoreceptor, UV RESISTANCE LOCUS 8 (UVR8) under natural conditions using a large-scale 'synchronized-genetic-perturbation-field-experiment'. Laboratory experiments have demonstrated a role for UVR8 in UV-B responses but do not reflect the complexity of outdoor conditions where 'genotype × environment' interactions can mask laboratory-observed responses. Arabidopsis thaliana knockout mutant, uvr8-7, and the corresponding Wassilewskija wild type, were sown outdoors on the same date at 21 locations across Europe, ranging from 39°N to 67°N latitude. Growth and climatic data were monitored until bolting. At the onset of bolting, rosette size, dry weight, and phenolics and glucosinolates were quantified. The uvr8-7 mutant developed a larger rosette and contained less kaempferol glycosides, quercetin glycosides and hydroxycinnamic acid derivatives than the wild type across all locations, demonstrating a role for UVR8 under field conditions. UV effects on rosette size and kaempferol glycoside content were UVR8 dependent, but independent of latitude. In contrast, differences between wild type and uvr8-7 in total quercetin glycosides, and the quercetin-to-kaempferol ratio decreased with increasing latitude, that is, a more variable UV response. Thus, the large-scale synchronized approach applied demonstrates a location-dependent functional role of UVR8 under natural conditions.
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| 25. |
- Palos, Mario F., et al.
(author)
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Electric Sail Mission Expeditor, ESME : Software Architecture and Initial ESTCube Lunar Cubesat E-Sail Experiment Design
- 2023
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In: Aerospace. - : MDPI AG. - 2226-4310. ; 10:8
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Journal article (peer-reviewed)abstract
- The electric solar wind sail, or E-sail, is a novel deep space propulsion concept which has not been demonstrated in space yet. While the solar wind is the authentic operational environment of the electric sail, its fundamentals can be demonstrated in the ionosphere where the E-sail can be used as a plasma brake for deorbiting. Two missions to be launched in 2023, Foresail-1p and ESTCube-2, will attempt to demonstrate Coulomb drag propulsion (an umbrella term for the E-sail and plasma brake) in low Earth orbit. This paper presents the next step of bringing the E-sail to deep space—we provide the initial modelling and trajectory analysis of demonstrating the E-sail in solar wind. The preliminary analysis assumes a six-unit cubesat being inserted in the lunar orbit where it deploys several hundred meters of the E-sail tether and charges the tether at 10–20 kV. The spacecraft will experience acceleration due to the solar wind particles being deflected by the electrostatic sheath around the charged tether. The paper includes two new concepts: the software architecture of a new mission design tool, the Electric Sail Mission Expeditor (ESME), and the initial E-sail experiment design for the lunar orbit. Our solar-wind simulation places the Electric Sail Test Cube (ESTCube) lunar cubesat with the E-sail tether in average solar wind conditions and we estimate a force of (Formula presented.) N produced by the Coulomb drag on a 2 km tether charged to 20 kV. Our trajectory analysis takes the 15 kg cubesat from the lunar back to the Earth orbit in under three years assuming a 2 km long tether and 20 kV. The results of this paper are used to set scientific requirements for the conceptional ESTCube lunar nanospacecraft mission design to be published subsequently in the Special Issue “Advances in CubeSat Sails and Tethers”.
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| 26. |
- Piovesan, Damiano, et al.
(author)
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DisProt 7.0 : a major update of the database of disordered proteins
- 2017
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:D1, s. d219-D227
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Journal article (peer-reviewed)abstract
- The Database of Protein Disorder (DisProt, URL: www.disprot.org) has been significantly updated and upgraded since its last major renewal in 2007. The current release holds information on more than 800 entries of IDPs/IDRs, i.e. intrinsically disordered proteins or regions that exist and function without a well-defined three-dimensional structure. We have re-curated previous entries to purge DisProt from conflicting cases, and also upgraded the functional classification scheme to reflect continuous advance in the field in the past 10 years or so. We define IDPs as proteins that are disordered along their entire sequence, i.e. entirely lack structural elements, and IDRs as regions that are at least five consecutive residues without well-defined structure. We base our assessment of disorder strictly on experimental evidence, such as X-ray crystallography and nuclear magnetic resonance ( primary techniques) and a broad range of other experimental approaches (secondary techniques). Confident and ambiguous annotations are highlighted separately. DisProt 7.0 presents classified knowledge regarding the experimental characterization and functional annotations of IDPs/IDRs, and is intended to provide an invaluable resource for the research community for a better understanding structural disorder and for developing better computational tools for studying disordered proteins.
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| 27. |
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| 28. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 29. |
- Santini, Sara, et al.
(author)
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Positive and Negative Impacts of Caring among Adolescents Caring for Grandparents : Results froman Online Survey in Six European Countries and Implications for Future Research, Policy and Practice
- 2020
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In: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 17:18, s. 1-16
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Journal article (peer-reviewed)abstract
- Although up to 8% of European youngsters carry out high-intensity care for a family member,adolescent young carers (AYCs), especially those caring for their grandparents (GrPs), remain anunder-researched group. This study aimed at addressing the current knowledge gap by carrying outan online survey in Italy, the Netherlands, Slovenia, Sweden, Switzerland, and the United Kingdom.The analysis included a final sample of 817 AYCs aged 15–17 years old. AYCs of grandparents (GrPs)were compared to AYCs of other care recipients (OCRs), in order to identify any dierence in positiveand negative caregiving outcomes and exposure factors between the two groups. Linear or logisticregression models were built, and multivariate analyses were repeated, including a fixed eect onthe country variable. AYCs of GrPs experienced more positive caregiving outcomes than AYCs ofOCRs across all six countries. Being female or non-binary, and having a migration background,were associated with more negative outcomes, regardless of the relationship with the care recipient.Further research on intergenerational caregiving outcomes is recommended for shaping measuresand policies, which preserve the intergenerational emotional bonds, whilst protecting AYCs frominappropriate responsibilities, undermining their mental health and well-being.
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| 30. |
- Stjern, Louise, et al.
(author)
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Cyclodextrin-mesoporous silica particle composites for controlled antibiotic release. A proof of concept toward colon targeting
- 2017
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In: International Journal of Pharmaceutics. - : Elsevier. - 0378-5173 .- 1873-3476. ; 531:2, s. 595-605
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Journal article (peer-reviewed)abstract
- Cyclodextrins (CDs) and mesoporous silica particles (MSPs) have been combined as composite carriers for controlled antibiotic release. CDs were employed as "gatekeeper" agents and grafted onto MSPs to retain drug molecules inside the MSP carrier. A variety of CDs (unfunctionalized, positively charged and carboxymethylated) and three different coupling strategies (covalent binding, electrostatic adsorption and inclusion complexation) were systematically investigated for their ability to control the release of two antibiotic drugs, metronidazole and clofazimine. The drugs had significantly different physicochemical properties (metronidazole - small hydrophilic, clofazimine- large hydrophobic). We report for the first time on the encapsulation and characterization of metronidazole-loaded-MSP. Each CD coating strategy reduced the drug release rate in phosphate buffer compared to unmodified MSP (from 20% to 100% retained drug). Covalent binding and inclusion complex approaches were significantly more effective than electrostatically adsorbed CD. In particular, the novel inclusion complex based on host/guest interaction between benzyl-modified silica surface and alpha-CD proved to be very effective (60-100% retained drug amount). Using pharmaceutical manufacturing processes, our study shows that CD-MSP composites can retain both hydrophobic and hydrophilic antibiotic compounds with potential translation to triggered release formulation targeting bacterial infections in the colon and lower intestine.
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| 31. |
- Thomsen, Hanna, 1989, et al.
(author)
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Increased antibiotic efficacy and noninvasive monitoring of Staphylococcus epidermidis biofilms using per-cysteamine-substituted γ-cyclodextrin - A delivery effect validated by fluorescence microscopy.
- 2020
-
In: International journal of pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 587
-
Journal article (peer-reviewed)abstract
- Limited and poor delivery of antibiotics is cited as one reason for the difficulty in treating antibiotic-resistant biofilms associated with chronic infections. We investigate the effectiveness of a positively charged, single isomer cyclodextrin derivative, octakis[6-(2-aminoethylthio)-6-deoxy]-γ-CD (γCys) to improve the delivery of antibiotics to biofilms. Using multiphoton laser scanning microscopy complemented with super-resolution fluorescence microscopy, we showed that γCys tagged with fluorescein (FITC) is uniformly distributed throughout live S. epidermidis biofilm cultures in vitro and results suggest it is localized extracellularly in the biofilm matrix. NMR spectroscopic data in aqueous solution confirm that γCys forms inclusion complexes with both the antibiotics oxacillin and rifampicin. Efficacy of γCys/antibiotic (oxacillin and rifampicin) was measured in the biofilms. While treatment with γCys/oxacillin had little improvement over oxacillin alone, γCys/rifampicin reduced the biofilm viability to background levels demonstrating a remarkable improvement over rifampicin alone. The strong synergistic effect for γCys/rifampicin is at this stage not clearly understood, but plausible explanations are related to increased solubility of rifampicin upon complexation and/or synergistic interference with components of the biofilm. The results demonstrate that designed cyclodextrin nanocarriers, like γCys, efficiently deliver suitable antibiotics to biofilms and that fluorescence microscopy offers a novel approach for mechanistic investigations.
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| 32. |
- Tunioli, Francesca, et al.
(author)
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Chemical Tailoring of β-Cyclodextrin-Graphene Oxide for Enhanced Per- and Polyfluoroalkyl Substances (PFAS) Adsorption from Drinking Water
- 2023
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In: Chemistry - A European Journal. - 1521-3765 .- 0947-6539. ; 29:60
-
Journal article (peer-reviewed)abstract
- We report on the synthesis of β-cyclodextrin (βCD) modified graphene oxide (GO) nanosheets, having different sized alkyl linkers (GO-Cn-βCD) and their exploitation as sorbent of per- and polyfluoroalkyl substances (PFAS) from drinking water. βCD were functionalized with a pending amino group, and the resulting precursors grafted to GO nanosheets by epoxide ring opening reaction. Loading of βCD units in the range 12 %–36 % was estimated by combined XPS and elemental analysis. Adsorption tests on perfluorobutanoic acid (PFBA), a particularly persistent PFAS selected as case study, revealed a strong influence of the alkyl linker length on the adsorption efficiency, with the hexyl linker derivative GO-C6-βCD outperforming both pristine GO and granular activated carbon (GAC), the standard sorbent benchmark. Molecular dynamic simulations ascribed this evidence to the favorable orientation of the βCD unit on the surface of GO which enables a strong contaminant molecules retention.
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| 33. |
- Vafaeian, Ghazaleh, 1982-
(author)
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Progressives in use and contact : A descriptive, areal and typological study with special focus on selected Iranian languages
- 2018
-
Doctoral thesis (other academic/artistic)abstract
- Progressives are grammatical patterns primarily used to refer to events that are ongoing at a specific time. This thesis investigates uses of such patterns in a number of languages as well as the interaction of a number of progressives in contact. The dissertation includes a typological study of the uses of 89 progressive patterns in two parallel corpora, an investigation of the uses and origin of the Persian dāštan progressive and an areal linguistic investigation of 50 Iranian varieties spoken around the Caspian Sea.The dissertation presents features that increase the likelihood that a progressive is used. Such features are 1) a focalized (punctual) reference point, 2) the engagement or ‘busyness’ of the agentive subject on the event, 3) an emotive component and 4) the desire to turn the attention of the addressee towards an ongoing event. The significance of these features is expected to weaken as progressives grammaticalize.There is a cross-linguistic tendency for progressives to occur more often with present time reference than with past time reference. In some cases, they are even restricted to the former. Among the varieties of the Iranian language Taleshi, on the other hand, we find asymmetric temporal paradigms as a consequence of former progressive patterns having expanded and lost their progressive character in the present but not in the past.The study also shows that progressives are used differently in the present and the past: while events with present time reference often have the features mentioned above in 1-4, events with past time reference are often, although not exclusively, background contexts to other events pushing the narration forward.The thesis also discusses various peripheral uses of progressives, such as uses in habitual and performative-like contexts, proximative, iterative and futurate uses, uses with stative verbs and temporary and subjective uses. Some of these tend to be found in patterns with higher frequencies and can be regarded as expansions towards the imperfective. Other uses are linked to the type of event to which the progressive applies: the proximative reading is shown to arise with achievements and the iterative use with repeated punctual events. The data from the varieties of the Iranian languages Mazandarani, Gilaki, Taleshi and Tati, as well as from varieties under the influence of Persian, suggests that the progressive in these varieties is highly borrowable. Among the varieties discussed in Chapter 5, an areal cline is noted where constructional schemas used for ongoing events shift towards the imperfective. In the borrowing process, on occasion, a shift from progressive to proximative is also noted. As expected, the data from Caspian varieties shows that there are more progressive patterns than imperfective patterns.
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| 34. |
- Wu, Zherui, et al.
(author)
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Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody
- 2019
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In: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 444, s. 147-161
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Journal article (peer-reviewed)abstract
- Overall survival of patients with metastatic non-small cell lung cancer (NSCLC) has significantly improved with platinum-based salt treatments and recently with targeted therapies and immunotherapies. However, treatment failure occurs due to acquired or emerging tumor resistance. We developed a monoclonal antibody against the proform of neurotensin (LF-NTS mAb) that alters the homeostasis of tumors overexpressing NTSR1. Neurotensin is frequently overexpressed along with its high affinity receptor (NTSR1) in tumors from epithelial origins. This ligand/receptor complex contributes to the progression of many tumor types by activation of the cellular effects involved in tumor progression (proliferation, survival, migration, and invasion). We demonstrate that LF-NTS mAb operates on the plasticity of tumor cells overexpressing NTSR1 and lowers their aggressiveness. The mAb enables the restoration of platinum-based therapies responsiveness, while also decreasing metastatic processes. Efficacy dosage with long-term treatment showed no obvious adverse events, while demonstrating improvement in the performance status. Our data suggests that LF-NTS mAb is an ideal candidate to be safely added to the conventional standard of care in order to improve its efficacy.
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| 35. |
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| 36. |
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